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At least 217 records · Page 12Linked to original sources
PubMed1994

Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation?

Allogeneic bone marrow transplantation (BMT) is associated with a severe complication--graft-versus-host disease (GVHD). Although effectively preventing GVHD, ex vivo T-lymphocyte marrow depletion unfortunately increases graft rejection and reduces the graft-versus-leukemia (GVL) effect. The ex vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T cells before their infusion with hematopoietic stem cells could allow for selective in vivo depletion of these T cells with ganciclovir (GCV) if subsequent GVHD was to occur. Thus, one could preserve the beneficial effects of the T cells on engraftment and tumor control in patients not experiencing severe GVHD. To obtain T cells specifically depleted by GCV, we transduced primary T cells with a retroviral vector containing the HS-tk and neomycin resistance (NeoR) genes. Gene transfer was performed by coculturing PHA +/- CD3- or alloantigen-stimulated purified T cells on an irradiated retroviral vector producer cell line or by incubating the T cells in supernatant from the producer. Subsequent culture in G418 for 1 week allowed for the selection of transduced cells. GCV treatment of interleukin-2-responding transduced and selected cells resulted in greater than 80% growth inhibition, whereas GCV treatment of control cells had no effect. Similarly, the allogeneic reactivity of HS-tk-transduced cells was specifically inhibited by GCV. Combining transduced and nontransduced T cells did not show a bystander effect, thus implying that all of the cells inhibited by GCV were indeed transduced. Lastly, studies involving the transduction of the HUT-78 (T-lymphoma) cell line suggest that stable expression of HS-tk can be maintained over 3 months in vitro in the absence of G418. In summary, we have established the feasibility of generating HS-tk-transduced T cells for subsequent in vivo transfer with hematopoietic stem cells and, if GVHD occurs, specific in vivo GCV-induced T-cell depletion in allogeneic BMT recipients.

Bone Marrow↗
PubMed1993

Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans.

TNF is effective in causing the regression of selected murine tumors when administered at high concentrations. Therapeutic levels in humans cannot be obtained systemically, however, because of dose-limiting toxicity. The development of immunotherapy with IL-2 and tumor-infiltrating lymphocytes (TIL), which can accumulate at tumor sites in some patients, and of efficient retroviral techniques for gene transfer into eukaryotic cells has allowed new therapeutic approaches using TNF. We have retrovirally transduced human TIL with the gene for TNF in an attempt to deliver high concentrations of TNF to the tumor site without dose-limiting systemic toxicity. Successful gene insertion was confirmed by Southern hybridization in 16 of 16 transduced and selected TIL cultures from 15 different patients, with an estimated 28 to 93% transduced cells within each culture. Transduced selected TIL cultures produced greater amounts of TNF, compared with nontransduced controls, in 11 of 16 cultures evaluated. However, overall production of TNF was > 30-fold lower, compared with a transduced and highly selected tumor cell line control (MEL-TNF). In addition, steady state levels of vector-derived transcript in nine of 10 transduced selected TIL cultures were < 14% of the amount seen in the MEL-TNF control line. In an attempt to increase TNF production, TIL were transduced with a mutated form of TNF containing the IFN-gamma signal peptide in place of the transmembranous region, to enhance secretion into the endoplasmic reticulum. By using this vector, TNF production increased by an average of fivefold. These studies demonstrate that TIL can be genetically modified to express and secrete a protein for use in targeted cancer therapy but that partial expression blockades exist that prevent maximal cytokine production by introduced genes in TIL.

DNA↗
PubMed1997

Thymidine kinase (TK) gene-transduced human lymphocytes can be highly purified, remain fully functional, and are killed efficiently with ganciclovir.

A graft-versus-leukemia (GVL) effect has been considered a major factor responsible for cures in patients with hematologic malignancies undergoing allogeneic bone marrow transplantation; however, associated graft-versus-host disease (GVHD) results in significant morbidity and mortality. T-cell depletion reduces the incidence and severity of GVHD but eliminates, at least partially, the GVL effect. Reinfusion of donor T lymphocytes at relapse posttransplantation can induce a potent antitumor response, but GVHD still occurs in the majority of patients. Prior transduction of T lymphocytes with the suicide gene, the viral thymidine kinase (TK), permits specific cell kill on administration of ganciclovir (GCV). Therefore, infusion of TK-transduced T lymphocytes may induce GVL effect and allow for their subsequent selective elimination in case GVHD develops. To evaluate the efficacy and feasibility of this promising approach, anti-CD3-stimulated primary human lymphocytes cultured in interleukin-2 were TK-transduced by a retroviral vector carrying both TK and neomycin-resistance genes. After selection in G418, more than 90% of the cells contained the TK gene as shown by a semiquantitative polymerase chain reaction. In addition, 1 to 5 days of GCV exposure, at clinically achievable concentrations of 20 to 50 micromol/L, induced > or = 90% killing of G418-selected cells without affecting nontransduced cells. Correlation of the extent of T-cell kill and the proportion of TK-gene-transduced cells is consistent with the absence of a bystander effect. Transduced cells were CD3+ and either CD8+ or CD4+ and retained functional properties of untransduced cells. In vivo administration of GCV prevented tumor development after subcutaneous injection of TK-transduced murine myeloma cells (MOPC-11), whereas such an effect was not observed on injection of untransduced cells into the opposite flank. Our studies provide critical information that (1) adequate numbers of TK-transduced lymphocytes can be selected efficiently with > or = 90% purity, (2) selected cells remain functional, (3) 24 hours of exposure to GCV at clinically achievable concentration effects > or = 90% killing of selected cells, and (4) GCV is effective in vivo in killing TK-transduced cells. Based on these data, a clinical study has been initiated in patients with multiple myeloma with persistent or relapsing disease after T-cell-depleted allogeneic transplants.

Animals↗
PubMed1997

Retroviral-mediated transfer of the green fluorescent protein gene into murine hematopoietic cells facilitates scoring and selection of transduced progenitors in vitro and identification of genetically modified cells in vivo.

We have investigated the utility of the green fluorescent protein (GFP) to serve as a marker to assess retroviral gene transfer into hematopoietic cells and as a tool to identify and enrich for cells expressing high levels of the vector-encoded transcript. GFP, by virtue of a naturally occurring chromophore encoded in its primary sequence, displays autonomous fluorescence, thus eliminating the need for antibody or cytochemical staining to detect its expression. A bicistronic murine stem cell virus (MSCV)-based retroviral vector was constructed containing the GFP cDNA and a mutant, human dihydrofolate reductase gene. High-titer, ecotropic retroviral producer cells free of replication competent virus were generated and used to transduce murine bone marrow cells by cocultivation. Within 24 hours after completion of the transduction procedure, a high proportion (40% to 70%) of the marrow cells were intensely fluorescent compared to mock-transduced cells or cells transduced with a control retrovirus. Erythroid and myeloid hematopoietic colonies derived from GFP-transduced marrow were easily scored for retroviral gene transfer by direct in situ fluorescence microscopy. Clonogenic progenitors expressing increased levels of antifolate drug resistance could be enriched from the GFP-transduced marrow population by fluorescence activated cell sorting of cells expressing high levels of GFP. In vivo, splenic hematopoietic colonies and peripheral blood cells from animals transplanted with GFP-transduced marrow displayed intense fluorescence. These results show that GFP is an excellent marker for scoring and tracking gene-modified hematopoietic cells and for allowing rapid selection and enrichment of transduced cells expressing high levels of the transgene.

Animals↗
PubMed1998

The endogenous calcium buffer and the time course of transducer adaptation in auditory hair cells.

Mechanoelectrical transducer currents in turtle auditory hair cells adapt to maintained stimuli via a Ca2+-dependent mechanism that is sensitive to the level of internal calcium buffer. We have used the properties of transducer adaptation to compare the effects of exogenous calcium buffers in the patch electrode solution with those of the endogenous buffer assayed with perforated-patch recording. The endogenous buffer of the hair bundle was equivalent to 0.1-0.4 mM BAPTA and, in a majority of cells, supported adaptation in an external Ca2+ concentration of 70 microM similar to that in turtle endolymph. The endogenous buffer had a higher effective concentration, and the adaptation time constant was faster in cells at the high-frequency end than at the low-frequency end of the cochlea. Experiments using buffers with different Ca2+-binding rates or dissociation constants indicated that the speed of adaptation and the resting open probability of the transducer channels could be differentially regulated and imply that the endogenous buffer must be a fast, high-affinity buffer. In some hair cells, the transducer current did not decay exponentially during a sustained stimulus but displayed damped oscillations at a frequency (58-230 Hz) that depended on external Ca2+ concentration. The gradient in adaptation time constant and the tuned transducer current at physiological levels of calcium buffer and external Ca2+ suggest that transducer adaptation may contribute to hair cell frequency selectivity. The results are discussed in terms of feedback regulation of transducer channels mediated by Ca2+ binding at two intracellular sites.

Animals↗
PubMed1988

Safe and cost-effective cleaning of pressure-monitoring transducers.

The CDC category I recommendation for high-level disinfection of pressure-monitoring transducers between uses imposes substantial costs. This practice has not been shown to be useful when disposable transducer domes are used. A prospective, randomized, double-blind study assessed the consequences of wiping transducers with alcohol between uses rather than sterilizing with ethylene oxide. We studied 5,197 transducer courses with disposable domes involving 2,202 patients in intensive care units during 15 months. There was no significant difference between the two treatment regimens in the risk of positive cultures of fluids from monitored lines, of cultures of cannula tips or of a positive blood culture. We conclude that under normal conditions, ie, in the absence of a cluster of transducer-related bacteremias, wiping transducers with alcohol between uses is sufficient when disposable domes are used.

Catheterization↗
PubMed1989

Epidemic bloodstream infections associated with pressure transducers: a persistent problem.

Twenty-four outbreaks of nosocomial bloodstream infection (BSI) were investigated by the Centers for Disease Control from Jan 1, 1977 to Dec 31, 1987. Intravascular pressure monitoring devices (transducers) were the most commonly identified source of bacterial and fungal BSI outbreaks and were implicated as the source of infection in eight (33%) outbreaks. These included outbreaks caused by Candida parapsilosis (2), Serratia marcescens (2), Klebsiella oxytoca (1), Pseudomonas cepacia (1), Acinetobacter calcoaceticus (1), and one polymicrobial bacteremia outbreak due to Acinetobacter, Pseudomonas, Citrobacter, and Enterobacter species. In all eight outbreaks, reusable transducers improperly disinfected or fitted with domes that had been improperly sterilized served as reservoirs for the organism. Compared with nosocomial BSI outbreaks not related to transducers, those in which transducers were implicated as a reservoir involved a larger mean number of patients (24 v 9; P = 0.007), and were significantly more likely to involve intensive care unit patients (23/24 v 3/9; P = 0.025) and to have a longer mean duration (11 v 3 months; P = 0.007). These findings show that the characteristics of transducer- and non-transducer-related BSI outbreaks differ, and that centers using intravascular pressure monitoring devices must be aware of and implement recommended infection control strategies for care and maintenance of these devices.

Catheters, Indwelling↗
PubMed1989

A correction procedure for the asymmetry of differential pressure transducers in respiratory impedance measurements.

The usual setup for measuring respiratory input impedance requires a differential pressure transducer attached to a pneumotachograph. As, up to now, no data correction procedure has been devised to account for transducer asymmetry, a highly symmetrical transducer is required to obtain reliable impedance data. In this communication, a general model for the measuring system is presented. Its main feature is that differential pressure transducers are modeled as two input-one output systems. From the theoretical model, we defined a dynamic calibration and data correction procedure. This was tested using highly asymmetrical transducers (common-mode rejection ratio between 45 and 27 dB) to measure the impedance of two respiratory analogs. The latter were linear resistance (R), inertance (I), compliance (C) series models simulating a normal subject (R = 3.47 hPa.s.l-1, I = 1.45 Pa.s2.l-1, C = 18.6 ml.hPa-1) and an obstructive patient (R = 11.15 hPa.s.l-1, I = 1.28 Pa.s2.l-1, C = 18.5 ml.hPa-1). Results obtained applying the devised procedure (errors in R, I, and C always less than 4 percent) show that respiratory input impedance can be adequately measured if data are corrected for transducer asymmetry.

Airway Resistance↗
PubMed1987

[Clinical experiences with a new reusable pressure transducer].

Invasive blood pressure monitoring is increasing in anesthesia and intensive care. Compared to noninvasive methods, it has some decisive advantages: (1) blood pressure trends can be assessed beat by beat, which is important especially in situations of cardiac arrhythmia; (2) respiratory changes in blood pressure as one sign of hypovolemia can be detected easily; and (3) pressure changes induced by the autonomic nervous system become apparent. We studied a new, reusable pressure transducer system, the Medex Novatrans-MX800 in routine intra- and postoperative monitoring of patients undergoing cardiac surgery using the following criteria: (1) handling; (2) accuracy of measurement; (3) durability; and (4) costs. The system is easy to use and has a low susceptability to breakdown. In 29 of 31 transducers tested, the error of measurement over a range of 0-150 mmHg was less than 2% as reported by the manufacturer. Two transducers showed errors of measurement over 5% after 60 times of reuse. The mean reusability rate until the transducer became defective was 75.8 +/- 17.3 in the operating room (19 transducers tested) and 59.7 +/- 29 in the intensive care unit (12 transducers tested, 11 still in use). A comparison of costs shows that the Novatrans-MX800 system is the cheapest system for invasive pressure monitoring available at this time.

Blood Pressure Determination↗
PubMed2003

Power requirements for vibrotactile piezo-electric and electromechanical transducers.

Human-machine information transfer through tactile excitation has addressed new applications in virtual reality, robotics, telesurgery, sensory substitution and rehabilitation for the handicapped in the past few years. Power consumption is an important factor in the design of vibrotactile displays, because it affects energy needs and the size, weight, heat dissipation and cost of the associated electronics. An experimental study is presented on the power required to reach tactile thresholds in electromechanical and piezo-electric transducers. Three different waveforms are considered, with an excitatory period formed by a burst of rectangular 50% duty cycle pulses (R50), rectangular low duty cycle pulses (RLO) and sinusoidal pulses (SIN). Ten different pulse repetition periods (RPs) were considered in the range 1/550-1/25 s. The voltage and current waveforms applied to the transducers at sensation thresholds in a group of 12 healthy subjects were sampled and stored in a digital oscilloscope. The average power was determined for each subject, and differences of two orders of magnitude were measured between the electromechanical and the piezo-electric transducer power consumption. Results show that, for the electromechanical transducer, a smaller power consumption of 25 microW was determined for RP = 1/25 s and the RLO waveform. In the case of the piezo-electric transducer, power of 0.21 microW was determined for SIN excitation and RP = 1/250 s. These results show the advantages of reducing power requirements for vibrotactile displays, which can be optimised by the choice of appropriate types of transducer, excitatory waveforms and pulse repetition periods.

Adult↗
PubMed1997

[An implantable piezoelectric hearing aid transducer for inner ear hearing loss. I: Development of a prototype].

Implantable hearing aids can form the basis of new surgical techniques for dealing with hearing problems originating in the inner ear, provided they are fully implantable. Accordingly, a comprehensive, interdisciplinary, combined project was initiated at the ENT clinic of the University of Tübingen which was to conclude with operations to improve hearing via fully implantable hearing aids. A novel electromechanical transducer for implantable hearing aids based on the piezoelectric principle is described. Unlike the piezoelectric transducers reported so far, this transducer does not rely on the bimorphic principle but on a circle-shaped, heteromorphic combination system consisting of a piezoceramic disc and metal membrane. The transducer can be hermetically sealed and is designed for implantation into the mastoid. Transfer of mechanical oscillations to an ossicle in the middle ear is effected by a directly fixed coupling rod or via suitable coupling elements. The transducer is highly tuned with a resonance frequency at the upper end of the spectral transfer range (greater than 10 kHz). Below this resonance and down to low frequencies, the frequency response of elongation is smooth with amplitudes of around 20 nm. At low and middle frequencies of up to 1 kHz, these vibration amplitudes correspond to sound-pressure levels of around 90 dB SPL. At higher frequencies of up to 10 kHz, the output level increases to about 130 dB SPL. Nonlinear distortions are also very small at the highest levels (less than 0.1%) throughout the whole transfer range. Electric power consumption at maximum levels is in the range of a few microwatts and is therefore significantly lower than that of electromagnetic systems. Particularly, this makes it possible to use the transducer in fully implantable hearing aids for rehabilitation of sensorineural hearing loss.

Cochlear Implants↗
PubMedDate not supplied

Comparison of measurements obtained with microtip and external water pressure transducers.

The aim of this study was to compare pressure readings obtained with catheter-mounted microtip and external water pressure transducers using a mechanical model for vesical pressure during Valsalva straining and coughing. The two catheter-mounted pressure transducers were simultaneously placed in a vinyl i.v. bag designed to mimic the parameters of the human bladder to allow comparison of simultaneous readings from both transducers. Simulated cough and Valsalva maneuvers of various strengths at different volumes (100 ml, 200 ml, 300 ml) were performed and the pressure readings generated by the two systems compared. The Pearson correlation coefficient between the systems was 0.998 for coughs and 0.998 for Valsalva efforts. Data were also analyzed by volume and strength of simulated cough and Valsalva effort, and correlations were found to be high (> or = 0.940) for all subgroup analyses. Mean absolute differences between events recorded by the two systems were small, as indicated by the y-intercept of 3.76 cmH2O pressure. Neither transducer recorded consistently higher pressures than the other. We concluded that there is a high correlation between pressure measurements obtained from microtip and external water pressure transducers during simulated cough and Valsalva efforts in this model. As similar correlation should exist in vivo, urodynamic data generated by the two transducer types should be comparable.

Cough↗
PubMed1981

Reproducibility of left ventricular internal dimensions with M mode echocardiography: effects of heart size, body position and transducer angulation.

Analysis was made of the variables of heart size, body position and transducer angle affecting the reproducibility of left ventricular internal dimensions as measured with M mode echocardiography. Echocardiograms were recorded in 24 subjects as the thorax was incrementally rotated and tilted. Transducer angle was noted from a three plane level attached to the probe. Constants were the technician, transducer placement and the interpreter. Heart rates varied insignificantly; respirations were held. Groups A and B were defined by their initial left ventricular internal dimensions at end-diastole (LVIDd): 49 +/- 5.9 and 73 +/- 8.6 mm (group mean +/- standard deviation). With body position constant the measurement error between duplicate recordings of LVIDd was +/- 1.2 mm (coefficient of variation = 1.8 percent) in Group A and +/- 4.5 mm (coefficient of variation = 4.6 percent) in Group B (p less than 0.001). Transducer angle varied 12 degrees between duplicate recordings in both groups. As the position of the thorax changed, the transducer followed, maintaining approximately the same incline with the chest wall. In both groups errors for combined LVIDd recorded with rotation and tilt, respectively, were unchanged from the duplication error. Thus, when the spatial orientation between the transducer and heart is held constant, it is the size of the heart that determines the reproducibility of the measurement of left ventricular internal dimensions.

Cardiac Volume↗
PubMed1996

Frequency content of normal and diabetic plantar pressure profiles: implications for the selection of transducer sizes.

How small do pressure transducers need to be in order to faithfully measure the plantar pressure profiles (PPPs) under normal and diabetic feet? In this study, pressures were collected from five diabetic and six non-diabetic subjects using a commercial measurement system with 25 mm2 transducers. Discrete Fourier Transform techniques were then used to determine (i) the spatial frequency content of diabetic and non-diabetic PPPs, and (ii) the effects of quadrupling the transducer area (from 5 mm x 5 mm to 10 mm x 10 mm). When the data were filtered to represent the effects of using 10 mm x 10 mm transducers, it was found that the ensuing reductions in peak pressure in the toe region (50 kPa) were significantly greater than in all other regions of the foot (p < 0.05). There was a significant correlation between pressure underestimations and measured peak pressures in the metatarsal regions. Based on data collected with 25 mm2 transducers it was concluded that transducer sizes greater than 6.36 mm x 6.18 mm (medio-lateral and antero-posterior directions) would result in sub-optimal sampling of PPPs.

Adult↗
PubMed1985

Optimization of ultrasonic transducers.

The so-called KLM-model for ultrasonic transducers is employed to optimize transducer design. Some new performance characteristics are defined which change monotonically with design parameters. These characteristics are based on the area of the envelope of the echo waveform produced by the transducer and of the corresponding amplitude spectrum. The efficiency of the transducer is defined by the round trip energy factor. The performance characteristics are used in a composite performance measure, which is then employed as a criterion in the optimization procedure. Two transducers are investigated: for medical imaging purposes and for spectral analysis of clinical echograms. The influence of electrical matching, backing impedance, matching layer impedance, bond line thickness and series induction on the optimized transducers is investigated.

Equipment Design↗
PubMed1993

Evaluation of a microsensor intracranial pressure transducer.

This report describes the results of a laboratory evaluation of a new device for monitoring intracranial pressure (ICP), consisting of a miniature pressure transducer mounted on a pressure sensing diaphragm. In in vitro tests, 6 microsensor transducers were monitored for drift at pressures of 10 mmHg and 20 mmHg. The maximal drift of any of the transducers was 1 mmHg over 9 days. In in vivo tests, the ICP measurement obtained with the microsensor transducer correlated well with pressures recorded from a catheter in the cisternal magna with a Statham transducer over a wide range of ICP values (n = 511, r = 0.998, P < 0.001). If these laboratory findings can be duplicated in clinical studies, this microsensor transducer may be a useful alternative to the ventriculostomy catheter and other currently used devices for monitoring ICP.

Animals↗
PubMed1992

A piezoelectric film transducer for dental occlusal analysis.

Occlusal load, contact sequence and location are necessary parameters for the study of dental biomechanics, simulation and clinical treatment planning. A piezoelectric film transducer for dental occlusal analysis was developed and in vitro evaluations of the transducer were conducted in a servohydraulically driven artificial mouth. The transducer is designed to provide occlusal contact force information. The transducer thickness (9 mum) minimizes interference with normal mandibular closure. Voltage outputs from the sensor as a result of occlusal contacts generated in the artificial mouth were sampled through a computer controlled data acquisition system. The transducer output recorded by the data acquisition system was calibrated to the applied load in the artificial mouth. The output of the piezoelectric film was evaluated during varying loads, cycling frequencies, surface areas of contact, and transducer surface areas. The preliminary studies indicate that the piezoelectric film holds out considerable promise and with further development may be well suited as a diagnostic tool in dental occlusal analysis.

Biomechanical Phenomena↗
PubMed1988

Variation of transducer frequency output and receiver band-pass characteristics for improved detection and image characterization of solid breast masses.

A new approach has been used for ultrasound detection of small benign and malignant breast masses, namely, control of scattering in such a manner that a small mass can be easily recognized because of the effect of the scattering on the contrast between the mass and the surrounding normal tissue. Maintenance of good resolution as scattering is varied is an essential aspect of this approach. Image contrast is dependent on a number of instrumentation parameters but, in a fundamental sense, it is related to differences in the amount of scattering between a solid breast mass and the surrounding normal tissue. In the subject studies, modification of image contrast is accomplished by varying either the center frequency output of the transducer or the band-pass of the receiver. These approaches take advantage of differences in the frequency dependence of scattering coefficients of solid breast masses and normal tissue. A unique technique for varying center frequency without switching transducers was developed, namely, use of a wide bandwidth, co-polymer PVDF transducer, in combination with certain instrumentation conditions which allow the center frequency output of a single ultrasound transducer to vary over a relatively wide frequency range. Using this technique, an automatic B-mode ultrasound imaging breast instrument which allows emission of 3.5, 4.5, 6.5 and 11 MHz ultrasound frequencies from the same co-polymer transducer was used to examine patients with solid breast masses. Both a wide band-pass receiver, similar to that commonly used in clinical ultrasound systems and a tunable receiver (which allows variation of the band-pass from wide to narrow) was used with this automated system. Using the standard receiver system, it was found that there are advantages to having a range of transducer frequencies immediately available for breast examination. These include: (1) improved detection of masses located in highly attenuating regions of breast (by decreasing frequency); (2) availability of diagnostically relevant information at some one frequency which may not be apparent at other frequencies. Using the multiple frequency system and the standard receiver, it was found that the most appropriate examination frequencies for detection and diagnosis of fibroadenomas are higher frequencies (8 to 11 MHz). This is particularly true in the case of fibroadenomas in fatty breasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenofibroma↗